布洛芬片加速试验.doc

布洛芬片 BP2010加速试验检验方法一、 鉴别A 片剂碾碎成粉后，取 0.5g 溶于 20ml 的丙酮中，过滤，流动空气脱水滤液（不要加热） ，收集残留物残留物的红外吸收图谱要与标准品吸收图谱一致（ Appendix II A；RS-186 ）B 石油醚重结晶后（沸点范围 40°到 60°）A 中残留物的熔点约为 75 摄氏度（ Appendix V A.） 二、 相关物质按照液相色谱方法（ Appendix III D），使用以下溶液：溶液 1 ：取已碾成粉的布洛芬片 0.2g，加 30ml 甲醇，振荡 30 分钟，再加入 30ml 甲醇后，用水定容到100ml，混匀，利用玻璃微孔滤纸（glass microfibre filter paper）过滤推荐 Whatman GF/C 这个型号的产品溶液 2：把溶液 1 用流动相介质稀释 100 倍溶液 3：用甲醇配置 0.006%w/v 的布洛芬杂质 B 标准品（欧洲标准）（可以使用 1 体积的杂质 B 欧洲标准品稀释到 10 体积来配置），使用 2.5ml 该溶液溶解 50mg 布洛芬英国药典标准品，甲醇定容到 25ml色谱条件A 使用不锈钢色谱柱（15 cm × 4.6 mm），利用色谱级球形封端十八烷基硅烷键合硅胶（5µm ） ，推荐使用 Spherisorb ODS 2 柱子。

B 使用无梯度洗脱和下文所述的流动相C 流速为 2ml/minD 常温柱温E 检测波长为 214nmF 上样量为 20µlG 在开始检测前先通 45 分钟流动相以稳定柱子H 保持总保留时间是主峰位置的 1.5 倍；如果按照前述条件设置色谱环境，布洛芬的保留时间大约是 20分钟流动相0.5 体积的正磷酸，340 体积的乙腈， 600 体积水，混匀平衡后，用水稀释到总共 1000 体积系统适应性使用溶液 3 得到的色谱峰，测量峰高 a：由 2-(4-butylphenyl)-propionic acid 产生的峰 2 - （4 - 苯基）丙酸和峰高 b：由布洛芬产生的峰；这两个峰的曲线最低点必须可以分离本实验不允许峰 a 大于 1.5 倍的峰 b如果有必要的话，可以通过调整乙腈的浓度来得到满足需要的溶液限制：1 由溶液 1 得到的色谱图：所有通过布洛芬杂质 B 得到的色谱图必须小于溶液 3 得到的色谱图0.3%）2 由溶液 2 得到的色谱图：每一个次高的色谱峰面积必须小于主峰面积的 0.3 倍0.3%）3 由溶液 2 得到的色谱图：所有次高的色谱峰面积的和，不包括杂质 B 产生的峰，必须小于主峰面积的0.7 倍。

0.7%）由溶液 2 得到的色谱图，忽略任何峰面积小于 0.1 倍的主峰的峰0.1%）三、 含量检测称重 20 片，使用液相色谱法 Appendix III D，使用下列溶液：1 0.2g 的布洛芬使用 30ml 的布洛芬振荡溶解 30 分钟，加流动相溶液到 100ml 混匀离心 25ml 溶液，转速为 2500 g，5 分钟，使用上清液2 使用 0.2%w/v 的布洛芬英国标准品色谱条件A 使用不锈钢色谱柱（25 cm × 4.6 mm），利用色谱级球形封端十八烷基硅烷键合硅胶（10µm） ，推荐使用 Nucleosil C18 柱子B 使用无梯度洗脱和下文所述的流动相C 流速为 1.5ml/minD 常温柱温E 检测波长为 264nmF 上样量为 20µl流动相3 体积的正磷酸，247 体积的水，750 体积的甲醇按照 C13H18O2 计算布洛芬的含量，在 95%-105%的含量为正常A. Extract a quantity of the powdered tablets containing 0.5 g of Ibuprofen with 20 ml of acetone , filter and evaporate the filtrate to dryness in a current of air without heating. The infrared absorption spectrum of the residue, Appendix II A, is concordant with the reference spectrum of ibuprofen (RS 186) .B. Melting point of the residue obtained in test A, after recrystallisation from petroleum spirit (boiling range, 40° to 60°), about 75°, Appendix V A.Related substancesCarry out the method for liquid chromatography , Appendix III D, using the following solutions. (1) Add 30 ml of methanol to a quantity of the powdered tablets containing 0.2 g of Ibuprofen, shake for 30 minutes, add 30 ml of methanol and sufficient water to produce 100 ml, mix and filter through a glass microfibre filter paper (Whatman GF/C is suitable).(2) Dilute 1 volume of solution (1) to 100 volumes with the mobile phase.(3) Dissolve 50 mg of ibuprofen BPCRS in 2.5 ml of a 0.006% w/v solution of Ibuprofen Impurity B EPCRS in methanol (prepared by diluting 1 volume of Ibuprofen Impurity B EPCRS to 10 volumes with methanol ) and add sufficient methanol to produce 25 ml.CHROMATOGRAPHIC CONDITIONS(a) Use a stainless steel column (15 cm × 4.6 mm) packed with end-capped octadecylsilyl silica gel for chromatography (5 µm) (Spherisorb ODS 2 is suitable).(b) Use isocratic elution and the mobile phase described below.(c) Use a flow rate of 2 ml per minute.(d) Use an ambient column temperature.(e) Use a detection wavelength of 214 nm.(f) Inject 20 µl of each solution.(g) Equilibrate the column with the mobile phase for about 45 minutes before starting the chromatography.(h) Allow the chromatography to proceed for 1.5 times the retention time of the principal peak. When the chromatograms are recorded under the conditions described above, the retention time of ibuprofen is about 20 minutes.MOBILE PHASE 0.5 volume of orthophosphoric acid , 340 volumes of acetonitrile and 600 volumes of water diluted to 1000 volumes with water after equilibration.SYSTEM SUITABILITYIn the chromatogram obtained with solution (3) measure the height (a) of the peak due to 2-(4-butylphenyl)-propionic acid and the height (b) of the lowest point of the curve separating this peak from that due to ibuprofen. The test is not valid unless a is greater than 1.5b. If necessary, adjust the concentration of acetonitrile in the mobile phase to obtain the required resolution.LIMITS In the chromatogram obtained with solution (1):the area of any peak corresponding to ibuprofen impurity B is not greater than the area of the corresponding peak in the chromatogram obtained with solution (3) (0.3%);the area of any other secondary peak is not greater than 0.3 times the area of the principal peak in the chromatogram obtained with solution (2) (0.3%);the sum of the area of any secondary peaks , other than the peak due to impurity B, is not greater than 0.7 times the area of the principal peak in the chromatogram obtained with solution (2) (0.7%).Disregard any peak the area of which is less than 0.1 times the area of the principal peak in the chromatogram obtained with solution (2) (0.1%).Weigh and powder 20 tablets. Carry out the method for liquid chromatography , Appendix III D, using the following solutions.(1) Shake a quantity of the powdered tablets containing 0.2 g of Ibuprofen with 30 ml of the mobile phase for 30 minutes, add sufficient o。